Implementation of microfluidic components, including molecular fractionation devices, in a microfluidic system

• US 7,094,345 B2
• Filed: 03/31/2004
• Issued: 08/22/2006
• Est. Priority Date: 09/09/2002
• Status: Expired due to Term

• Current Assignee: Cytonome/St, Llc (Cytonome Inc.)
• Original Assignee: Cytonome Inc.
• Inventors: Deshpande, Manish, Gilbert, John R., Trikha, Jaishree
• Primary Examiner(s): Walker, W. L.
• Assistant Examiner(s): Menon, Krishnan S
• Application Number:
  US10/816,514
• Publication Number:
  US 20040245102A1
• Time in Patent Office: 874 Days
• Field of Search: 210/632, 210/635, 210/321.6, 210/85, 204/450, 422/101, 422/104, 977/DIG.1
• US Class Current: 210/321.61
• CPC Class Codes: B01D 2313/13 Specific connectors
• CPC Class Codes: B01D 2313/40 Adsorbents within the flow path
• CPC Class Codes: B01D 2325/028 Microfluidic pore structures
• CPC Class Codes: B01D 2325/12 Adsorbents being present on the surface of the membranes or in the pores
• CPC Class Codes: B01D 63/087 Single membrane modules
• CPC Class Codes: B01D 63/088 Microfluidic devices comprising semi-permeable flat membranes
• CPC Class Codes: B01D 67/0034 by micromachining techniques, e.g. using masking and etching steps, photolithography
• CPC Class Codes: B01D 67/0062 by micromachining techniques, e.g. using masking and etching steps, photolithography
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/028 Modular arrangements
• CPC Class Codes: B01L 2200/146 Employing pressure sensors
• CPC Class Codes: B01L 2300/041 Connecting closures to device or container
• CPC Class Codes: B01L 2300/047 Additional chamber, reservoir
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0874 Three dimensional network
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0655 pinch valves
• CPC Class Codes: B01L 2400/0666 Solenoid valves
• CPC Class Codes: B01L 3/06 : Crystallising dishes
• CPC Class Codes: B01L 3/502707 : characterised by the manufacture of the container or its components by shaping or joining plastic parts B29C59/00, B29C65/00; by laminating B32B37/00; manufacture of microstructural devices in general B81C
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502753 : characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• CPC Class Codes: C02F 2209/36 : Biological material, e.g. enzymes or ATP
• CPC Class Codes: C30B 29/58 : Macromolecular compounds
• CPC Class Codes: C30B 7/00 : Single-crystal growth from solutions using solvents which are liquid at normal temperature, e.g. aqueous solutions from molten solvents C30B9/00; by normal or gradient freezing C30B11/00; under a protective fluid C30B27/00
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44773 : Multi-stage electrophoresis, e.g. two-dimensional electrophoresis
• CPC Class Codes: Y10S 977/786 : Fluidic host/matrix containing nanomaterials
• CPC Class Codes: Y10T 156/10 : Methods of surface bonding and/or assembly therefor

Abstract

A system and method for integrating microfluidic components in a microfluidic system enables the microfluidic system to perform a selected microfluidic function. A capping module includes a microfluidic element for performing a microfluidic function. The capping module is stacked on a microfluidic substrate having microfluidic plumbing to incorporate the microfluidic function into the system. The microfluidic element may comprise a matrix having an affinity for selected molecules in a sample. The matrix binds, reacts with and/or retains the selected molecules without affecting other molecules in the sample.

Claims

1. A microfluidic system, comprising:

a first microchannel formed in a substrate;

a first communication port coupling the first microchannel to a surface of the substrate; and

a capping module forming a chamber and having a matrix having an affinity for selected molecules disposed in the chamber and a trapping filter forming a sidewall of the chamber for compartmentalizing the matrix on the capping module, wherein the trapping filter includes a semipermeable membrane that is permeable to fluids and impermeable to the matrix, wherein the capping module is adapted to be stacked on the substrate and placed in communication with the first microchannel, the capping module further comprising a first connector port extending through the semipermeable membrane for placing the chamber in fluid communication with the first communication port, and a second connector port extending through the semipermeable membrane for connecting the chamber in fluid communication with a second communication port that couples a second microchannel to a surface of the substrate, thereby forming a fluid path between the first microchannel and the second microchannel.

2. The system of claim 1, wherein the matrix comprises an array of affinity beads for selectively binding to the selected molecule.

3. The system of claim 2, wherein the affinity beads are coated with binding sites configured to bind to the selected molecules.

4. The system of claim 1, wherein the matrix includes an enzyme for reacting with the selected molecules.

5. The system of claim 1, wherein the matrix includes detection molecules that react with a sample to produce a measurable reaction.

6. The system of claim 1, further comprising a capillary electrophoresis column coupled to the second microchannel.

7. The system of claim 1, further comprising an impermeable layer covering the semipermeable membrane, wherein the impermeable layer does not cover the first and second connector port to allow liquid flow through the first and second connector port.

8. A capping module for a microfluidic system, comprising:

a substrate forming a recess;

a matrix disposed in the recess on the substrate, the matrix having an affinity for selected molecules,

a trapping filter, including a semipermeable membrane, covering the recess to form a chamber for compartmentalizing the matrix on the substrates,

a first connector port extending through the semipermeable membrane for placing the chamber in communication with a first microchannel,

a second connector port for placing the chamber in communication with a second microchannel,

a third connector port for placing the chamber in communication with a third microchannel, and

a fourth connector port for placing the chamber in communication with a fourth microchannel.

9. The capping module of claim 8, wherein the substrate includes the first and second connector port formed therein.

10. The capping module of claim 8, wherein:

the first microchannel, the chamber and the second microchannel form a first fluid path, and

the third microchannel, the chamber and the fourth microchannel form a second fluid path.

11. A molecular fractionation device for a microfluidic system, comprising:

a capping module comprising a substrate defining a region for holding a matrix,

a trapping filter for compartmentalizing a matrix on the substrate;

a first connector port for placing the region for holding a matrix in fluid communication with an exterior of the substrate and a first microchannel, wherein the trapping filter covers the connector port, and the first connector port includes a valve for selectively blocking flow through the first connector port,

a second connector port for placing the region for holding the matrix in communication with a second microchannel, including a valve for selectively blocking flow through the second connector port,

a third connector port for placing the region for holding the matrix in communication with a third microchannel, including a valve for selectively blocking flow through the third connector port, and

a fourth connector port for placing the region for holding the matrix in communication with a fourth microchannel, including a valve for selectively blocking flow through the fourth connector port.

12. The molecular fractionation device of claim 11, further comprising a matrix insertion port in communication with the region for holding a matrix for inserting a matrix into the substrate.

13. A microfluidic system, comprising:

a first channel for conveying a sample; and

a plurality of molecular fractionation devices coupled to the channel and arranged in series, such that a first outlet of a first molecular fractionation device is in communication with a first inlet of a second molecular fractionation device, wherein each molecular fractionation device includes a matrix having an affinity for a selected set of molecules, wherein the matrix is disposed in a chamber having a sidewall defined by a trapping filter including a semipermeable membrane.

14. The system of claim 13, further comprising a release channel connected to a second outlet of one of said molecular fractionation devices.

15. The system of claim 13, wherein each molecular fractionation device further includes two outlets, wherein the system further comprises a plurality of release channels, each release channel being connected to a second outlet of one of the molecular fractionation devices.

16. The system of claim 15, wherein each molecular fractionation device further includes two inlets for providing a buffer solution to the matrix.

17. The system of claim 16, further comprising a filtration system coupled to one of said release channels.

18. The system of claim 17, wherein the filtration system comprising a capping module having a membrane for performing a filtering a sample, wherein the capping module is adapted to be stacked on the substrate and placed in communication with the release channel.

19. The system of claim 17, further comprising a capillary electrophoresis column coupled to the filtration system.

20. The system of claim 13, further comprising an ejection component for ejecting a sample fraction from the system.

21. A molecular fractionation device, comprising

capping module having a chamber for holding a matrix having an affinity for selected molecules,

a trapping filter including a semipermeable membrane for compartmentalizing the matrix in the chamber,

a first connector port for placing the chamber in communication with a first microchannel,

a second connector port for placing the chamber in communication with a second microchannel,

a third connector port for placing the chamber in communication with a third microchannel,

a fourth connector port for placing the chamber in communication with a fourth microchannel, and

at least one valve for selectively blocking fluid flow through one of said connector ports.

22. The molecular fractionation device of claim 21, further comprising a sealable matrix insertion port formed in the chamber for inserting the matrix into the chamber.